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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁博煌 | zh_TW |
| dc.contributor.advisor | Po-Huang Liang | en |
| dc.contributor.author | 黃韋凱 | zh_TW |
| dc.contributor.author | Wei-Kai Huang | en |
| dc.date.accessioned | 2024-07-23T16:11:52Z | - |
| dc.date.available | 2024-07-24 | - |
| dc.date.copyright | 2024-07-23 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-19 | - |
| dc.identifier.citation | 1. Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.;Shi. W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G. F.; Tan,W. China novel coronavirus investigating and research team. A novel coronavirus frompatients with pneumonia in China, 2019. N. Engl. J. Med. 2020, 382 (8), 727–733, DOI:10.1056/NEJMoa2001017
2. Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.;Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.;Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao,B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet 2020, 395 (10223), 497–506, DOI: 10.1016/S0140-6736(20)30183-5 3. Gordon, C. J.; Tchesnokov, E. P.; Woolner, E.; Perry, J. K.; Feng, J. Y.; Porter, D.P.; Götte, M. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNApolymerase from Severe Acute Respiratory Syndrome Coronavirus 2 with high potency.J. Biol. Chem. 2020, 295 (20), 6785–6797, DOI: 10.1074/jbc.RA120.013679 4. Grein, J.; Ohmagari, N.; Shin, D.; Diaz, G.; Asperges, E.; Castagna, A.; Feldt, T.;Green, G.; Green, M. L.; Lescure, F. 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Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicaseinhibitors: a systematic review of in vitro studies. J. Virus Erad. 2023, 9(2), 100327.DOI: 10.1016/j.jve.2023.100327 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93187 | - |
| dc.description.abstract | 嚴重急性呼吸系統綜合症冠狀病毒-2（SARS-CoV-2）是造成 2019 年全球冠狀病毒病（COVID-19）的病原體，造成數百萬人死亡並對生活產生重大影響。病毒非結構蛋白 13（NSP13）解旋酶利用 ATP 水解的能量在 5' 至 3' 方向上解開雙鏈 DNA 或 RNA，由於其在病毒複製中的關鍵作用，已被確定為一個具有發展性的靶標。在這篇論文中，我表達純化了重組 SARS-CoV-2 解旋酶。通過使用孔雀石綠檢測磷酸鹽的 ATP 酶活性，確定了先前發現可抑制多種抗 SARS-CoV-2 靶標的內部 FDA 批准藥物或化學合成化合物和天然化合物對解旋酶的抑制活性。並採用分子對接技術闡明 SARS-CoV-2 解旋酶抑製劑的構效關係。此外，我還使用了 3109 個 FDA 核准的藥物庫、201 個動物用藥物、3200 個解旋酶標靶庫等，以虛擬方式篩選出解旋酶潛在抑製劑。測定了這些化合物的半抑制濃度 IC50，並通過對接程式對複雜結構進行了建模，以提供結構原理。綜合上述，本研究找出了一些可能的 SARS-CoV-2 解旋酶 ATP 水解活性的抑製劑，為對抗 COVID-19 提供了潛在的策略。 | zh_TW |
| dc.description.abstract | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the global coronavirus disease 2019 (COVID-19) pandemic, causing millions of people death and significant impact on life. The viral non-structural protein 13 (NSP13) helicase, which uses energy from NTP hydrolysis to unwind double-stranded DNA or RNA in a 5' to 3' direction, has been recognized as a promising target due to its essential role in viral replication. In this thesis, the recombinant SARS-CoV-2 helicase was expressed and purified. By assaying its ATPase activity using malachite green to detect phosphate, the inhibitory activities of the in house potential compounds and natural compounds previously found to inhibit several anti-SARS-CoV-2 targets were determined. Molecular docking was employed to elucidate the binding modes of the inhibitors against SARS-CoV-2 helicase. Furthermore, three compound libraries were used to virtually screen out helicase potential inhibitors. In conclusion, this study identifies promising inhibitors of SARS CoV-2 helicase, offering potential strategies for combating COVID-19. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-07-23T16:11:52Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-07-23T16:11:52Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract iv 1. Introduction 1 2. Materials and Methods 4 2.1 Materials 4 2.2 SARS-COV-2 NSP13 expression 4 2.3 SARS-COV-2 NSP13 purification 4 2.4 SARS-CoV-2 helicase ATPase kinetics and inhibitory assay 5 2.5 Virtual screening–calculating binding energy 7 2.6 Molecular docking-binding modes 8 3. Results 9 3.1 Purification and characterization of the recombinant SARS-CoV-2 NSP13 helicase 9 3.2 Assays of the helicase ATPase kinetics 9 3.3 Chemical structures of the tea polyphenol-related natural products 10 3.4 Test of the selected natural products for inhibiting NSP13 11 3.5 Binding modes of the active natural product inhibitors with NSP13 12 3.6 Test of the in-house compounds for inhibiting NSP13 15 3.7 Binding modes of the active in-house compounds with NSP13 16 3.8 Virtual screening of the chemical libraries for finding NSP13 inhibitors 17 4. Discussion 19 5. Tables 26 Table 1. Inhibitory effects of the selected natural products against NSP13 and SARS-CoV-2 26 Table 2. Inhibitory effects of the active in-house compounds against NSP13 ....28 Table 3. Virtually screened out potential inhibitors against NSP13 using the FDA-approved Drug Library (3109 compounds) from Selleck Chemicals 29 Table 4. Inhibitory effects of the virtually screened out FDA-approved drugs against NSP13 30 Table 5. Virtually screened out potential inhibitors against NSP13 using the Helicase Targeted Library (3200 compounds) from Life Chemicals 31 Table 6. Virtually screened out potential inhibitors against NSP13 using the Animal drugs (201 compounds) 34 6. Figures 35 Figure 1. Purification of the recombinant SARS-CoV-2 NSP13 36 Figure 2. The assay method for the NSP13 ATPase activity 37 Figure 3. Chemical structures of some selected natural products 39 Figure 4. Inhibitory effects of the selected natural products against NSP13 41 Figure 5. Computer modeled binding modes of the active natural products in NSP13 43 Figure 6. Comparison of the binding modes of the active natural products 46 Figure 7. Chemical structures of the active in-house compounds 47 Figure 8. Inhibitory effects of the active in-house compounds against NSP13 48 Figure 9. Binding modes of the active in-house compounds in NSP13 49 Figure 10. Virtual screening of the chemical libraries for finding NSP13 inhibitors 50 Figure 11. Chemical structure of the virtually screened out FDA-approved drugs as NSP13 inhibitors 51 Reference 52 | - |
| dc.language.iso | en | - |
| dc.subject | 嚴重急性呼吸系統綜合症冠狀病毒-2 | zh_TW |
| dc.subject | 病毒非結構蛋白 13 解旋酶 | zh_TW |
| dc.subject | 半抑制濃度 | zh_TW |
| dc.subject | 分子對接技術 | zh_TW |
| dc.subject | 抑製劑 | zh_TW |
| dc.subject | Molecular docking | en |
| dc.subject | SARS-CoV-2 | en |
| dc.subject | non-structural protein 13 helicase | en |
| dc.subject | malachite green | en |
| dc.subject | inhibitors | en |
| dc.title | SARS-CoV-2 NSP13 解旋酶 ATP 活性抑制劑的篩選 | zh_TW |
| dc.title | Screening of SARS-CoV-2 NSP13 helicase ATPase inhibitors | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 謝俊結;張淑媛 | zh_TW |
| dc.contributor.oralexamcommittee | Jiun-Jie Shie;Sui-Yuan Chang | en |
| dc.subject.keyword | 嚴重急性呼吸系統綜合症冠狀病毒-2,病毒非結構蛋白 13 解旋酶,半抑制濃度,分子對接技術,抑製劑, | zh_TW |
| dc.subject.keyword | SARS-CoV-2,non-structural protein 13 helicase,malachite green,Molecular docking,inhibitors, | en |
| dc.relation.page | 62 | - |
| dc.identifier.doi | 10.6342/NTU202401680 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-07-19 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科學研究所 | - |
| 顯示於系所單位： | 生化科學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-112-2.pdf 未授權公開取用 | 1.99 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。